- 作者：Saba Sile ; Niloufar B. Gillani ; Digna R. Velez ; Carlos G. Vanoye ; Chang Yu ; Loretta M. Byrne ; James V. Gainer ; Nancy J. Brown ; Scott M. Williams ; Alfred L. George Jr
- 关键词：BSND ; renal chloride channel ; hypertension ; protective alleles ; modifier gene
- 刊名：American Journal of Hypertension
- 出版年：2007
- 出版时间：November 2007
- 年：2007
- 卷：20
- 期：11
- 页码：1176-1182.e1
- 全文大小：160 K
Background
Defects in the handling of renal salt reabsorption may contribute to interindividual differences in blood-pressure regulation and susceptibility to hypertension. Sodium chloride reabsorption in the thick ascending limb (TAL) is dependent in part on the chloride channel, ClC-Kb (encoded by CLCNKB), and its accessory subunit, barttin (encoded by BSND).Methods
We investigated genetic variations in BSND in a screening population, and genotyped a homogenous cohort of normotensive and hypertensive Ghanaian subjects, in addition to four ethnically defined control populations. Functional consequences of the identified BSND variants were examined using a heterologous expression system.
Results
Three novel, nonsynonymous coding-sequence single-nucleotide polymorphisms were identified (V43I, E255Q, and G284D) in the screening population. BSND-V43I was identified in African American, Asian, and Hispanic subjects, with minor allele frequencies of 0.14, 0.18, and 0.01, respectively, but it was absent in the Caucasian population. BSND-E225Q and BSND-G284D were rare variants. Two of these variants (V43I and G284D) exhibited partial loss-of-function phenotypes when heterologously expressed with ClC-Kb chloride channels in cultured cells. In logistic regression analyses, we observed no association between hypertension and BSND-I43 in our study population. However, we did observe significant deviation from Hardy-Weinberg equilibrium in the normotensive population.
Conclusions
We conclude that BSND-V43I, a common variant conferring partial loss of function, exhibits significant deviation from Hardy-Weinberg equilibrium in the Ghanaian normotensive control population. However, it does not independently confer protection against hypertension.